1、August 2010 Translation by DIN-Sprachendienst.English price group 11No part of this translation may be reproduced without prior permission ofDIN Deutsches Institut fr Normung e. V., Berlin. Beuth Verlag GmbH, 10772 Berlin, Germany,has the exclusive right of sale for German Standards (DIN-Normen).ICS
2、 11.040.20!$j*“1712907www.din.deDDIN EN ISO 8536-2Infusion equipment for medical use Part 2: Closures for infusion bottles (ISO 8536-2:2010)English translation of DIN EN ISO 8536-2:2010-08Infusionsgerte zur medizinischen Verwendung Teil 2: Stopfen fr Infusionsflaschen (ISO 8536-2:2010)Englische bers
3、etzung von DIN EN ISO 8536-2:2010-08Matriel de perfusion usage mdical Partie 2: Bouchons pour flacons de perfusion (ISO 8536-2:2010)Traduction anglaise de DIN EN ISO 8536-2:2010-08SupersedesDIN EN ISO 8536-2:2003-02 andDIN EN ISO 8536-2Corrigendum 1:2005-06www.beuth.deIn case of doubt, the German-la
4、nguage original shall be considered authoritative.Document comprises 19 pages08.10 DIN EN ISO 8536-2:2010-08 2 A comma is used as the decimal marker. National foreword This standard has been prepared by Technical Committee ISO/TC 76 “Transfusion, infusion and injection equipment for medical and phar
5、maceutical use” (Secretariat: DIN, Germany) in collaboration with CEN Management Centre (CMC). The responsible German body involved in its preparation was the Normenausschuss Medizin (Medical Standards Committee), Working Committee NA 063-02-15 AA Gummi. DIN EN ISO 8536 consists of the following par
6、ts, under the general title Infusion equipment for medical use: Part 1: Infusion glass bottles Part 2: Closures for infusion bottles Part 3: Aluminium caps for infusion bottles Part 4: Infusion sets for single use, gravity feed Part 8: Infusion equipment for use with pressure infusion apparatus Part
7、 9: Fluid lines for use with pressure infusion equipment Part 10: Accessories for fluid lines for use with pressure infusion equipment Part 11: Infusion filters for use with pressure infusion equipment Further, the DIN ISO 8536 standards series consists of the following parts, under the general titl
8、e Infusion equipment for medical use: Part 5: Burette infusion sets for single use, gravity feed Part 6: Freeze drying closures for infusion bottles Part 7: Caps made of aluminium-plastics combinations for infusion bottles Part 12: Check valves The DIN Standards corresponding to the International St
9、andards referred to in this document are as follows: ISO 48 DIN ISO 48 ISO 3302 (all parts) DIN ISO 3302 (all parts) ISO 8536-1 DIN EN ISO 8536-1 ISO 8871-1 DIN EN ISO 8871-1 ISO 8871-4 DIN EN ISO 8871-4 ISO 8871-5 DIN ISO 8871-5 ISO 15378 DIN EN ISO 15378 Amendments This standard differs from DIN E
10、N ISO 8536-2:2003-02 and DIN EN ISO 8536-2 Corrigendum 1:2005-06 as follows: a) The scope now expressly states that the dimensional requirements are not applicable to barrier-coated closures. b) Requirements relating to materials and stability (clauses 5 and 6) have been revised. ISO 8536-3 DIN ISO
11、8536-3 DIN EN ISO 8536-2:2010-08 3 c) Subclause 6.4 “Biological requirements” makes reference to ISO 8871-4. d) The standard (including the content of Corrigendum 1:2003) has been revised in form and substance. e) The standard has been editorially revised. Previous editions DIN ISO 8536-2:1993-04 DI
12、N EN ISO 8536-2:2003-02 DIN EN ISO 8536-2 Corrigendum 1:2005-06 DIN 58363-2: 1974-11, 1978-03 DIN 58363-6: 1974-11, 1978-03 DIN 58363-10: 1974-11, 1978-03 DIN 58363-11: 1974-11, 1978-03 DIN 58363-12: 1975-08 DIN 58367-1: 1975-08, 1984-04, 1986-04 National Annex NA (informative) Bibliography DIN ISO
13、48, Rubber, vulcanized or thermoplastic Determination of hardness (hardness between 10 IRHD and 100 IRHD) DIN ISO 3302 (all parts), Rubber Tolerances for products DIN ISO 8536-2, Infusion equipment for medical use Part 3: Aluminium caps for infusion bottles DIN ISO 8871-5, Elastomeric parts for pare
14、nterals and for devices for pharmaceutical use Part 5: Functional requirements and testing DIN EN ISO 8536-1, Infusion equipment for medical use Part 1: Infusion glass bottles DIN EN ISO 8871-1, Elastomeric parts for parenterals and for devices for pharmaceutical use Part 1: Extractables in aqueous
15、autoclavates DIN EN ISO 8871-4, Elastomeric parts for parenterals and for devices for pharmaceutical use Part 4: Biological requirements and test methods DIN EN ISO 15378, Primary packaging materials for medicinal products Particular requirements for the application of ISO 9001:2000, with reference
16、to Good Manufacturing Practice (GMP) DIN EN ISO 8536-2:2010-08 4 This page is intentionally blank EUROPEAN STANDARD NORME EUROPENNE EUROPISCHE NORM EN ISO 8536-2 March 2010 ICS 11.040.20 Supersedes EN ISO 8536-2:2002English Version Infusion equipment for medical use - Part 2: Closures for infusion b
17、ottles (ISO 8536-2:2010) Matriel de perfusion usage mdical - Partie 2: Bouchons pour flacons de perfusion (ISO 8536-2:2010) Infusionsgerte zur medizinischen Verwendung - Teil 2: Stopfen fr Infusionsflaschen (ISO 8536-2:2010) This European Standard was approved by CEN on 18 February 2010. CEN members
18、 are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this European Standard the status of a national standard without any alteration. Up-to-date lists and bibliographical references concerning such national standards may be obtained on application
19、to the CEN Management Centre or to any CEN member. This European Standard exists in three official versions (English, French, German). A version in any other language made by translation under the responsibility of a CEN member into its own language and notified to the CEN Management Centre has the
20、same status as the official versions. CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland,
21、 Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and United Kingdom. EUROPEAN COMMITTEE FOR STANDARDIZATION COMIT EUROPEN DE NORMALISATION EUROPISCHES KOMITEE FR NORMUNG Management Centre: Avenue Marnix 17, B-1000 Brussels 2010 CEN All rights of exploitation in any form and by any
22、means reserved worldwide for CEN national Members. Ref. No. EN ISO 8536-2:2010: EContents DIN EN ISO 8536-2:2010-08 EN ISO 8536-2:2010 (E) 2 Page Foreword3 Introduction .4 1 Scope 5 2 Normative references 5 3 Shape and dimensions5 4 Designation 7 5 Material .7 6 Requirements.7 6.1 General7 6.2 Physi
23、cal requirements 7 6.3 Chemical requirements .8 6.4 Biological requirements8 7 Labelling .8 Annex A (normative) Determination of fragments.9 Annex B (normative) Determination of spike penetration force 11 Annex C (normative) Spike retention/sealability .13 Annex D (normative) Closure piercing device
24、 .14 Bibliography 15 Foreword This European Standard shall be given the status of a national standard, either by publication of an identical text or by endorsement, at the latest by September 2010, and conflicting national standards shall be withdrawn at the latest by September 2010. Attention is dr
25、awn to the possibility that some of the elements of this document may be the subject of patent rights. CEN and/or CENELEC shall not be held responsible for identifying any or all such patent rights. This document supersedes EN ISO 8536-2:2002. According to the CEN/CENELEC Internal Regulations, the n
26、ational standards organizations of the following countries are bound to implement this European Standard: Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlan
27、ds, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and the United Kingdom. Endorsement notice The text of ISO 8536-2:2010 has been approved by CEN as a EN ISO 8536-2:2010 without any modification. This document (EN ISO 8536-2:2010) has been prepared by Technical Co
28、mmittee ISO/TC 76 “Transfusion, infusion and injection equipment for medical and pharmaceutical use”. DIN EN ISO 8536-2:2010-08 EN ISO 8536-2:2010 (E) 3 Introduction The purpose of this part of ISO 8536 is to specify the shape and dimensions of and the requirements for elastomeric closures intended
29、for infusion bottles. In order to provide seal integrity of the container closure systems the dimensions of the elastomeric closures have to be compatible with the dimensions of the infusion bottles and the caps as specified in corresponding parts of ISO 8536. Primary packaging components made of el
30、astomeric materials are an integral part of medicinal products and thus the principles of current Good Manufacturing Practice (cGMP) apply to the manufacturing of these components. Principles of cGMP are described in, e.g. ISO 15378 or GMP Guidelines as published by the European Community and the Un
31、ited States of America. DIN EN ISO 8536-2:2010-08 EN ISO 8536-2:2010 (E) 4 1 Scope This part of ISO 8536 specifies the shape, dimensions, material, performance requirements and labelling of closures for infusion bottles as specified in ISO 8536-1. The dimensional requirements are not applicable to b
32、arrier-coated closures. Closures specified in this part of ISO 8536 are intended for single use only. NOTE The potency, purity, stability and safety of a medicinal product during its manufacture and storage can strongly be affected by the nature and performance of the primary packaging. 2 Normative
33、references The following referenced documents are indispensable for the application of this document. For dated references, only the edition cited applies. For undated references, the latest edition of the referenced document (including any amendments) applies. ISO 48, Rubber, vulcanized or thermopl
34、astic Determination of hardness (hardness between 10 IRHD and 100 IRHD) ISO 3302-1, Rubber Tolerances for products Part 1: Dimensional tolerances ISO 3302-2, Rubber Tolerances for products Part 2: Geometrical tolerances ISO 7619-1, Rubber, vulcanized or thermoplastic Determination of indentation har
35、dness Part 1: Durometer method (Shore hardness) ISO 8536-1, Infusion equipment for medical use Part 1: Infusion glass bottles ISO 8536-3, Infusion equipment for medical use Part 3: Aluminium caps for infusion bottles ISO 8871-1, Elastomeric parts for parenterals and for devices for pharmaceutical us
36、e Part 1: Extractables in aqueous autoclavates ISO 8871-4, Elastomeric parts for parenterals and for devices for pharmaceutical use Part 4: Biological requirements and test methods 3 Shape and dimensions 3.1 The shape and dimensions of closures shall be as shown in Figure 1 and as given in Table 1.
37、Figure 1 illustrates two typical designs of closure, types A and B. DIN EN ISO 8536-2:2010-08 EN ISO 8536-2:2010 (E) 5 Dimensions in millimetres Figure 1 Dimensions and configuration of type A and type B closures Table 1 Dimensions of infusion closures Dimensions in millimetres Type Nominal size d1
38、0,2 d2max. d3min. d4min. d5max. d60,3 h10,4 h20,3 h3h4a0,3 h5A 32 23,6 18,2 13 13 14 30,8 12,2 4 5,1 4 B 28 19,6 15,5 6,9 6,1 7,1 27,1 10,2 3,4 4,2 2,5 5,1 aIndentations may reduce the piercing thickness. 3.2 If not otherwise specified, general dimensional tolerances shall be in accordance with ISO
39、3302-1 and ISO 3302-2. 3.3 In order to facilitate the production process, the flange of the closure may have a slightly conical shape (maximum 0,8 mm related to the diameter). The trimming edge of the flange shall comply with the tolerances specified for the diameter of the flange. 3.4 The diameter,
40、 d4, which defines the piercing area shall not exceed d3. Marks and indentations may be placed in the piercing area. The height of the marks shall not exceed 0,3 mm. DIN EN ISO 8536-2:2010-08 EN ISO 8536-2:2010 (E) 6 NOTE The spacers in Figure 1 for type A and type B closures are shown for illustrat
41、ive purposes only and do not form part of the requirements of this part of ISO 8536. 3.5 All edges of the closure may be rounded. 4 Designation Closures can be designated according to their type, see Figure 1. The designation is expressed as the number of this part of ISO 8536 followed by the nomina
42、l size of the infusion bottle followed by the type letter. EXAMPLE A type A closure for infusion bottles of nominal size 32 mm complying with the requirements laid down in this part of ISO 8536 is designated as follows: Infusion closure ISO 8536-2 - 32 - A 5 Material The elastomeric material used sh
43、all meet the requirements specified in Clause 6. The elastomeric material shall withstand two sterilization cycles when autoclaving in saturated steam at (121 2) C for 30 min without exceeding the specified limits and without the impairment of its performance characteristics under the conditions of
44、normal use. In case of other sterilization methods, e. g. irradiation, the suitability of the material shall be evaluated. NOTE For use with infusion solutions, resistance to two steam sterilization cycles may not be needed because only terminal sterilization is applied. Closures shall be made of el
45、astomeric formulation originally tested and approved by the end-user. The closure manufacturer shall ensure the conformance of each delivery with the type sample and the compliance with previously agreed functional parameters and compendium requirements. 6 Requirements 6.1 General The requirements s
46、pecified in 6.2 to 6.4 represent minimum requirements which refer to the condition of the elastomeric closures on receipt by the user. 6.2 Physical requirements 6.2.1 Hardness The hardness agreed between manufacturer and user shall not differ from the nominal value by more than 5 Shore A when tested
47、 in accordance with ISO 7619-1 on a special test specimen. Alternatively, the hardness can be tested on the closures according to ISO 48. If tested according to ISO 48, the microhardness shall not differ by more than 5 IRHD from the type sample. 6.2.2 Fragmentation When tested for fragmentation in a
48、ccordance with Annex A, not more than 20 fragments of diameter W 50 m per 10 piercings shall be observed. DIN EN ISO 8536-2:2010-08 EN ISO 8536-2:2010 (E) 7 6.2.3 Spike penetration force When tested for penetrability in accordance with Annex B, the force needed to penetrate the closure shall not exc
49、eed 80 N, and the average value shall be less than 75 N. No closure shall be pushed into the bottle during piercing. 6.2.4 Spike retention/sealability When tested in accordance with Annex C, complete penetration shall be achieved (no closure shall be pushed into the bottle) in all cases and no signs of leakage shall appear between the spike and the closure over 4 h; nor shall the spike be pulled from the closure during this time period. 6.2.5 Resistance to ageing The maxim
